Structural Chemistry of Human SET Domain Protein Methyltransferases
Matthieu Schapira*, 1, 2
1 Structural Genomics Consortium, University of Toronto, MaRS Centre, Toronto, Ontario, M5G 1L7, Canada
2 Department of Pharmacology and Toxicology, University of Toronto, Medical Sciences Building, Toronto, Ontario, M5S 1A8, Canada
Abstract
There are about fifty SET domain protein methyltransferases (PMTs) in the human genome, that transfer a methyl group from S-adenosyl-L-methionine (SAM) to substrate lysines on histone tails or other peptides. A number of structures in complex with cofactor, substrate, or inhibitors revealed the mechanisms of substrate recognition, methylation state specificity, and chemical inhibition. Based on these structures, we review the structural chemistry of SET domain PMTs, and propose general concepts towards the development of selective inhibitors.
Keywords: Methyltransferase, SET domain, structure, PMT, histone, epigenetics.
Article Information
Article History:
Received Date: 27/1/2011
Revision Received Date: 6/4/2011
Acceptance Date: 25/4/2011
Electronic publication date: 22/8/2011
Collection year: 2011
© Matthieu Schapira; Licensee Bentham Open.
open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (
http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.
* Address correspondence to this author at the Structural Genomics Consortium, University of Toronto, MaRS Centre, Toronto, Ontario, M5G 1L7, Canada; Tel: 416-978-3092; Fax: 416-946-0880; E-mail: matthieu.schapira@utoronto.ca
Open Peer Review Details |
Manuscript submitted on 27-1-2011 |
Original Manuscript |
Structural Chemistry of Human SET Domain Protein Methyltransferases |